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Xia T.-S.,Nanjing Medical University | Wang J.,Nanjing Medical University | Yin H.,Nanjing Medical University | Ding Q.,Nanjing Medical University | And 9 more authors.
Oncology Reports | Year: 2010

An ideal mouse model should closely mimic a clinical situation. However, for most models available, this is not the case since clinical trials frequently fail to reproduce the highly encouraging therapeutic results obtained from preclinical studies performed using mouse models. In this study, in the process of extending the application of our previously established breast tissue-derived orthotopic and metastatic (BOM) model, the human breast cancer cell line MDA-MB-231 failed to exhibit any osteotropic features that differed from previous studies. Our observations suggest that a human tissue-specific microenvironment could be an essential requirement for a successful mouse model of breast cancer. Here, multiple in vivo breast cancer models were used to confirm this hypothesis. Human breast tissue and cancellated bone were transplanted subcutaneously to female severe combined immunodeficiency disease (SCID) mice by different assemblies, to build several mouse models termed 'breast-breast', 'breast-bone', 'bone-bone', 'MFP (mouse mammary fat pad)-bone', and 'MFP-breast' models. Two human breast cancer cell lines, MDA-MB-231 and MDA-MB-231BO, and the mouse breast cancer cell line TM40D were used. All cancer cells were labeled with GFP for gross observation. In addition, transplanted human tissues and various mouse tissues including bone, lung, liver, mesentery were examined microscopically. Based on morphological, immunohistochemical, and enzymohistochemical evidence obtained from several comparative experiments in 'breast-breast', 'breast-bone' and 'bone-bone' models, the BOM model was proved to be feasible and reliable. The organ tropism of the breast cancer cell line, which was derived from a mouse model by intracardiac inoculation in a pure mouse microenvironment, was reconsidered. The behavior of breast cancer cells in the mouse model was altered in response to the varying microenvironment. The results in this study suggest the human tissue-specific microenvironment is most likely an essential requirement in mouse models of breast cancer.

Geater S.L.,Prince of Songkla University | Xu C.-R.,Guangdong Lung Cancer Institute | Zhou C.,Tongji University | Hu C.-P.,Central South University | And 11 more authors.
Journal of Thoracic Oncology | Year: 2015

Introduction: In the phase III, LUX-Lung 6 trial, afatinib prolonged progression-free survival (PFS) versus cisplatin/gemcitabine in Asian patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). This article provides detailed assessments of patient-reported outcomes (PROs), a LUX-Lung 6 secondary end point, and explores the relationship between PFS and health-related quality of life (QoL) in these patients. Methods: Patients (n = 364) were randomized (2:1) to oral afatinib (40 mg/day) or up to six cycles of cisplatin/gemcitabine (21-day cycle; cisplatin 75 mg/m2 [d1]; gemcitabine 1000 mg/m2 [d1,8]). QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and its lung cancer-specific module. The relationship between PFS (investigator assessment and independent review) and QoL was evaluated using analysis of covariance and a longitudinal model. Results: More patients treated with afatinib versus cisplatin/gemcitabine showed improvements in global health status/QoL (p < 0.0001) and physical (p < 0.0001), role (p = 0.013), and social (p < 0.001) functioning scales. Delayed symptom deterioration and better QoL over time was also observed with afatinib. QoL measured before tumor assessment was considerably poorer for patients with progression than those without progression, with significant differences in mean scores at multiple assessment time points. Results from the longitudinal analysis consistently demonstrated a significant negative impact of progression on QoL (p < 0.0001). Conclusion: Afatinib improved PFS and PROs versus chemotherapy in EGFR mutation-positive NSCLC patients. Progression was associated with statistically significant worsening in QoL measured before tumor assessment, underscoring the value of PFS as a clinically relevant end point. © 2015 by the International Association for the Study of Lung Cancer.

Wu Y.-L.,Guangdong General Hospital and Guangdong Academy of Medical science | Zhou C.,Shanghai Pulmonary Hospital | Hu C.-P.,Central South University | Feng J.,Jiangsu Provincial Tumor Hospital | And 11 more authors.
The Lancet Oncology | Year: 2014

Background: Afatinib-an oral irreversible ErbB family blocker-improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin-a chemotherapy regimen widely used in Asia-for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC. Methods: This open-label, randomised phase 3 trial was done at 36 centres in China, Thailand, and South Korea. After central testing for EGFR mutations, treatment-naive patients (stage IIIB or IV cancer [American Joint Committee on Cancer version 6], performance status 0-1) were randomly assigned (2:1) to receive either oral afatinib (40 mg per day) or intravenous gemcitabine 1000 mg/m2 on day 1 and day 8 plus cisplatin 75 mg/m2 on day 1 of a 3-week schedule for up to six cycles. Randomisation was done centrally with a random number-generating system and an interactive internet and voice-response system. Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three). Clinicians and patients were not masked to treatment assignment, but the independent central imaging review group were. Treatment continued until disease progression, intolerable toxic effects, or withdrawal of consent. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01121393. Findings: 910 patients were screened and 364 were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin). Median progression-free survival was significantly longer in the afatinib group (11·0 months, 95% CI 9·7-13·7) than in the gemcitabine and cisplatin group (5·6 months, 5·1-6·7; hazard ratio 0·28, 95% CI 0·20-0·39; p<0·0001). The most common treatment-related grade 3 or 4 adverse events in the afatinib group were rash or acne (35 [14·6%] of 239 patients), diarrhoea (13 [5·4%]), and stomatitis or mucositis (13 [5·4%]), compared with neutropenia (30 [26·5%] of 113 patients), vomiting (22 [19·5%]), and leucopenia (17 [15·0%]) in the gemcitabine and cisplatin group. Treatment-related serious adverse events occurred in 15 (6·3%) patients in the afatinib group and nine (8·0%) patients in the gemcitabine and cisplatin group. Interpretation: First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population. Funding: Boehringer Ingelheim. © 2014 Elsevier Ltd.

Tian W.,Sun Yat Sen University | Wang Z.,Sun Yat Sen University | Zhou J.,Hunan Provincial Tumor Hospital | Zhang S.,Beijing Institute of Thoracic Cancer and Tuberculosis | And 8 more authors.
Medical Oncology | Year: 2011

The objective of this study was to compare the efficacy and tolerability of palonosetron and granisetron in a Chinese population receiving highly emetogenic cisplatin-based chemotherapy or moderately emetogenic chemotherapy. Patients were stratified by chemotherapy with cisplatin (yes/no) and then randomly assigned to receive either palonosetron (0.25 mg i.v.) in the first cycle followed by granisetron (3 mg i.v.) in the second cycle or vice versa. The primary efficacy endpoint was the proportion of patients with complete response 0-24 h post-chemotherapy administration. The proportions of patients with complete response 24-120 and 0-120 h following chemotherapy were also compared. Of the 144 patients randomized, 36 (25%) received 60-80 mg/m2 cisplatin; 66 of 72 patients in the palonosetron to granisetron group and 56 of 72 patients in the granisetron to palonosetron group completed treatment with both antiemetics. The efficacy and safety analyses included 128 palonosetron treatments and 138 granisetron treatments. Palonosetron consistently produced numerically higher complete response rates than granisetron in the acute phase (0-24 h, 71.09 vs. 65.22%), the delayed phase (24-120 h, 60.16 vs. 55.80%), and overall (0-120 h, 53.13 vs. 50.00%) though the differences were not significant. Both palonosetron and granisetron were well tolerated. Palonosetron was well tolerated and effective in preventing acute and delayed chemotherapy-induced nausea and vomiting in a Chinese population. When used as monotherapy, 0.25-mg palonosetron was not inferior to 3-mg granisetron for preventing vomiting following highly or moderately emetogenic chemotherapy. © 2010 Springer Science+Business Media, LLC.

Yuan P.,Jianhu Peoples Hospital of Jiangsu | Yue T.-H.,Jianhu Peoples Hospital of Jiangsu | Xiao Y.-H.,Jianhu Peoples Hospital of Jiangsu | Zhu L.-J.,Jiangsu Provincial Tumor Hospital | And 2 more authors.
World Chinese Journal of Digestology | Year: 2014

Aim: To assess the clinical effects of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of gastric cancer with malignant ascites.Methods: Seventy patients with gastric cancer with malignant ascites were randomly divided into either a study group or a control group. The study group was treated by HIPEC combined with thermal therapy, and the control group was treated by non-hyperthermic peritoneal perfusion chemotherapy. The clinical effects, Kamofsky score and adverse reactions were compared for the two groups. The temperature and vital signs at different points of HIPEC were recorded.Results: The total effective rate was significantly higher in the experiment group than in the control group (77.14% vs 37.14%, P < 0.05). Posttreatment Kamofsky scores for the two groups were significantly higher than prior-treatment values (77.92 ± 6.83 vs 54.44 ± 5.47, 62.08 ± 6.17 vs 53.89 ± 5.56, P < 0.05). Posttreatment Kamofsky score was significantly higher in the experiment group than in the control group (77.92 ± 6.83 vs 62.08 ± 6.17, P < 0.05). There were no significant difference in the shell temperature, tympanic temperature, rectal temperature, blood pressure, heart rate, breath, or oxyhemoglobin saturation for the experiment group at different time points (36.18 °C ± 0.42 °C vs 36.42 °C ± 0.27 °C vs 37.13 °C ± 1.72 °C, 35.66 °C ± 0.23 °C vs 35.94 °C ± 0.37 °C vs 36.60 °C ± 0.22 °C, 36.34 °C ± 0.12 °C vs 36.64 °C ± 0.27 °C vs 37.10 °C ± 0.30 °C, 117 mmHg ± 6.2 mmHg vs 116 mmHg ± 6.5 mmHg vs 116 mmHg ± 6.4 mmHg, 62 mmHg ± 4.9 mmHg vs 69 mmHg ± 6.8 mmHg vs 72 mmHg ± 5.3 mmHg, 68/min ± 4.3/min vs 72/ min ± 5.3/min vs 73/min ± 4.5/min, 14/min ± 2.5/min vs 13/min ± 1.8/min vs 14/min ± 1.7/min, 98% ± 1.8% vs 97% ± 0.9% vs 98% ± 1.3%, P > 0.05). The rate of fatty scleroma for the experiment group was significantly higher than that for the control group (14.29% vs 0.00%, P < 0.05).Conclusion: HIPEC can improve Kamofsky score and has high safety in patients with gastric cancer with malignant ascites. © 2014 Baishideng Publishing Group Inc. All rights reserved.

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